Comparison of short-read and long-read amplicon and metagenomic sequencing data from clinical microbiome samples

Human microbiome profiling relies largely on short-read DNA sequencing. Accurate sequencing and analysis is essential for accurate microbiome profiling, which is critical for the development of novel microbiome-targeted therapeutics. Recent improvements in long-read sequencing technology provide a promising, but more expensive, alternative to short-read sequencing. To our knowledge, improved high fidelity long-read sequencing has not been applied to clinical microbiome samples in comparison to short-read sequencing. Using samples from participants in a Phase 1b trial of a novel live biotherapeutic, we compare microbiome profiles generated from short-read and long-read sequencing for amplicon-based 16S profiling and metagenomic sequencing.